US 11,807,618 B2
Thiophene derivatives as antiviral agents
Eric Meldrum, Riehen (CH); Benoît De Chassey, Lyons (FR); Laëtitia Lines, Villeurbanne (FR); Jérôme Amaudrut, Dijon (FR); Benaissa Boubia, Saint Apollinaire (FR); Vincent Derain, Prenois (FR); Fabrice Guillier, Belleneuve (FR); Christian Montalbetti, Fontaine-les-Dijon (FR); Calum Macleod, Bishop's Stortford (GB); Karine Fabienne Malagu, Cambridge (GB); David Robert Vesey, Harlow (GB); and Paul Colin Michael Winship, Cambridge (GB)
Assigned to ENYO PHARMA, Lyons (FR)
Filed by ENYO PHARMA, Lyons (FR)
Filed on Mar. 18, 2022, as Appl. No. 17/697,981.
Application 17/697,981 is a division of application No. 16/473,660, granted, now 11,279,683, previously published as PCT/EP2017/084726, filed on Dec. 28, 2017.
Claims priority of application No. 16306843 (EP), filed on Dec. 29, 2016.
Prior Publication US 2022/0213053 A1, Jul. 7, 2022
Int. Cl. C07D 333/78 (2006.01); A61P 31/12 (2006.01); C07D 333/38 (2006.01); C07D 333/68 (2006.01); C07D 409/12 (2006.01); C07D 413/12 (2006.01); C07D 417/12 (2006.01); C07D 493/08 (2006.01); C07D 495/04 (2006.01)
CPC C07D 333/78 (2013.01) [A61P 31/12 (2018.01); C07D 333/38 (2013.01); C07D 333/68 (2013.01); C07D 409/12 (2013.01); C07D 413/12 (2013.01); C07D 417/12 (2013.01); C07D 493/08 (2013.01); C07D 495/04 (2013.01)] 7 Claims
 
1. A compound having the following formula (I):

OG Complex Work Unit Chemistry
wherein:
R1 and R2 form together a 5-7 membered ring, saturated or unsaturated,
said 5-7 membered ring comprises one or more heteroatoms selected from the group consisting of:
N, optionally substituted by a radical selected from the group consisting of
a (C1-C6)alkyl, a (C2-C6)alkenyl, a (C2-C6)alkynyl,
a 5-10 membered ring, saturated or unsaturated, selected from the group consisting of cycloalkyl, aryl, heterocycloalkyl, and heteroaryl,
a saturated or unsaturated (C1-C6)alkylcycloalkyl, (C1-C6)alkylaryl, (C1-C6)alkylheterocycloalkyl), or (C1-C6)alkylheteroaryl, and
a CO—(C1-C6)alkyl, a CO2—(C1-C6)alkyl, a CO—(C1-C6)alkylaryl, a CO-aryl, a CO-heteroaryl, a SO2-aryl, or a SO2-heteroaryl,
said radical is optionally substituted by at least one —OH, halogen, (C1-C6)alkyl, or (C1-C6)alkyloxy,
 O, and
 S, and
said 5-7 membered ring is optionally substituted by:
a (C1-C6)alkyl, a (C2-C6)alkenyl, a (C2-C6)alkynyl, optionally substituted by at least one halogen, or —OH,
a 5-10 membered ring, saturated or unsaturated, selected from the group consisting of cycloalkyl, aryl, heterocycloalkyl, and heteroaryl,
a saturated or unsaturated (C1-C6)alkylcycloalkyl, (C1-C6)alkylaryl, (C1-C6)alkylheterocycloalkyl), or (C1-C6)alkylheteroaryl,
 a halogen, —CN, or —NO2,
C(O)R, —C(O)2R, —C(O)NRR′, —CONHOR, —CONHSO2R, —NRR′, —N(R)C(O)R′, —N(R)NR′R″, —N(R)C(O)2R′, —N(R)C(O)NR′R″, —N(R)S(O)2R′, —OR, —SR, —S(O)R, —S(O2)R, —S(O)NRR′, or —S(O)2NRR′, R, R′, and R″ being independently H, (C1-C6)alkyl, cycloalkyl, aryl, heterocycloalkyl, heteroaryl, (C1-C6)alkylcycloalkyl, (C1-C6)alkylaryl, (C1-C6)alkylheterocycloalkyl), (C1-C6)alkylheteroaryl, or R and R′ or R′ and R″ may form a 5-7 membered ring, optionally interrupted by one or several heteroatoms, said 5-7 membered ring is optionally substituted by at least one —OH, halogen, (C1-C6)alkyl or (C1-C6)alkyloxy;
R3 represents:
a cyclohexyl being substituted in vicinal position with respect to the CO of the —NH—CO—R3 group by at least one group (A) selected from the group consisting of: —C(O)R, —C(O)2R, —C(O)NRR′, —CONHOR, and —CONHSO2R, R and R′ are as defined above;
R4 represents a radical selected from the group of:
a 5-14 membered ring, saturated or unsaturated, selected from the group consisting of a cycloalkyl, an aryl, a heterocycloalkyl, a heteroaryl, a fused arylheterocycloalkyl, and a fused arylcycloalkyl, and
a (C1-C6)alkylcycloalkyl, a (C1-C6)alkylaryl, a (C1-C6)alkylheterocycloalkyl, and a (C1-C6)alkylheteroaryl, and
a (C1-C6)alkyl,
said radicals being optionally substituted by at least one group (B) selected from the group consisting of:
a (C1-C6)alkyl or a (C1-C6)alkoxy, optionally substituted by at least one OH, one halogen or one —NRR′, R, R′, and R″ are as defined above,
a halogen, —CN, or —NO2,
a 5-10 membered ring, saturated or unsaturated, selected from the group consisting of a cycloalkyl, an aryl, a heterocycloalkyl, and a heteroaryl, optionally substituted by at least one OH, one halogen, one (C1-C6)alkyl, one (C1-C6)alkyloxy or one —NRR′, R, R′, and R″ are as defined,
a saturated or unsaturated (C1-C6)alkylcycloalkyl, (C1-C6)alkylaryl, (C1-C6)alkylheterocycloalkyl, or (C1-C6)alkylheteroaryl, optionally substituted by at least one —OH, halogen, (C1-C6)alkyl, or (C1-C6)alkyloxy,
—C(O)R, —C(O)2R, —C(O)NRR′, —CONHOR, —CONHSO2R, —NRR′, —N(R)C(O)R′, —N(R)NR′R″, —N(R)C(O)2R′, —N(R)C(O)NR′R″, —N(R)S(O)2R′, —OR, —SR, —S(O)R, —S(O2)R, —S(O)NRR′, or —S(O)2NRR′, R, R′, and R″ are as defined above; and
R5 represents H, a (C1-C6)alkyl, a (C2-C6)alkenyl, or a (C2-C6)alkynyl; or
R4 and R5 may form together a 5-14 membered ring, optionally interrupted by one or several heteroatoms, said 5-14 membered ring is optionally substituted by at least one —OH, halogen, (C1-C6)alkyl, (C1-C6)alkyloxy, cycloalkyl, or a 5-10 membered ring selected from the group of an aryl, a heterocycloalkyl, and a heteroaryl, optionally substituted by at least one —OH, halogen, (C1-C6)alkyl, or (C1-C6)alkyloxy;
and the pharmaceutical salts thereof.